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Quantification of mRNA in Lipid Nanoparticles Using Mass Spectrometry



Mark Lowenthal, Abigail Antonishek, Karen W. Phinney


Lipid nanoparticle-encapsulated messenger RNA (LNP-mRNA) holds great promise as a novel modality for treating a broad range of diseases. The ability to quantify mRNA accurately in therapeutic products helps to ensure consistency and safety. Here we consider one important aspect of accuracy, measurement traceability, which establishes trueness in quantity. Previous work established a quantitative approach for oligonucleotide measurements through an accounting of any oligomer's fundamental nucleobases (e.g. A, C, T, G, U) using a common nucleobase traceability chain. In this study, LNP-mRNA quantity is measured in situ using a liquid chromatography-mass spectrometry (LC-MS) approach. The analysis does not require mRNA extraction or detergents and is achieved through direct acid hydrolysis of LNP-mRNA prior to an isotope dilution strategy, resulting in accurate quantitative analysis of mRNA independent of time or place. Acid hydrolysis LC-MS is shown to be amenable to measuring both active substance or formulated mRNA drug product – both critical attributes of mRNA-based therapeutics development.
(potentially a different journal, still TBD)


mRNA, lipid nanoparticles, mRNA-LNP, quantification, biomanufacturing, mass spectrometry, isotope dilution


Lowenthal, M. , Antonishek, A. and Phinney, K. (2023), Quantification of mRNA in Lipid Nanoparticles Using Mass Spectrometry, (potentially a different journal, still TBD), [online],, (Accessed June 16, 2024)


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Created December 26, 2023, Updated January 8, 2024